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Q64536

- PDK2_RAT

UniProt

Q64536 - PDK2_RAT

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Protein

[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial

Gene
Pdk2
Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

Serine/threonine kinase that plays a key role in the regulation of glucose and fatty acid metabolism and homeostasis via phosphorylation of the pyruvate dehydrogenase subunits PDHA1 and PDHA2. This inhibits pyruvate dehydrogenase activity, and thereby regulates metabolite flux through the tricarboxylic acid cycle, down-regulates aerobic respiration and inhibits the formation of acetyl-coenzyme A from pyruvate. Inhibition of pyruvate dehydrogenase decreases glucose utilization and increases fat metabolism. Mediates cellular responses to insulin. Plays an important role in maintaining normal blood glucose levels and in metabolic adaptation to nutrient availability. Via its regulation of pyruvate dehydrogenase activity, plays an important role in maintaining normal blood pH and in preventing the accumulation of ketone bodies under starvation. Plays a role in the regulation of cell proliferation and in resistance to apoptosis under oxidative stress. Plays a role in p53/TP53-mediated apoptosis.5 Publications

Catalytic activityi

ATP + [pyruvate dehydrogenase (acetyl-transferring)] = ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate.6 Publications

Enzyme regulationi

Activity increases in response to increased acetyl-CoA and NADH levels and upon binding to the pyruvate dehydrogenase subunit DLAT. Inhibited by ADP and pyruvate; these compounds interfere with DLAT binding and thereby inhibit kinase activity. Inhibited by dichloroacetate. Inhibited by AZD7545; this compound interferes with DLAT binding and thereby inhibits kinase activity. Reactive oxygen species cause the formation of disulfide bonds, and thereby inhibit the enzyme.2 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei290 – 2901ATP

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi251 – 2588ATP
Nucleotide bindingi309 – 3102ATP
Nucleotide bindingi325 – 3306ATP

GO - Molecular functioni

  1. ATP binding Source: RGD
  2. protein complex binding Source: RGD
  3. protein heterodimerization activity Source: RGD
  4. protein homodimerization activity Source: RGD
  5. protein serine/threonine kinase activity Source: UniProtKB
  6. pyruvate dehydrogenase (acetyl-transferring) kinase activity Source: UniProtKB

GO - Biological processi

  1. cellular response to nutrient Source: UniProtKB
  2. glucose homeostasis Source: UniProtKB
  3. glucose metabolic process Source: UniProtKB-KW
  4. insulin receptor signaling pathway Source: UniProtKB
  5. peptidyl-serine phosphorylation Source: UniProtKB
  6. protein phosphorylation Source: RGD
  7. regulation of acetyl-CoA biosynthetic process from pyruvate Source: UniProtKB
  8. regulation of cellular ketone metabolic process Source: UniProtKB
  9. regulation of gluconeogenesis Source: UniProtKB
  10. regulation of glucose metabolic process Source: UniProtKB
  11. regulation of pH Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Carbohydrate metabolism, Glucose metabolism

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial (EC:2.7.11.2)
Alternative name(s):
PDK P45
Pyruvate dehydrogenase kinase isoform 2
Short name:
PDH kinase 2
Gene namesi
Name:Pdk2
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Unplaced

Organism-specific databases

RGDi69428. Pdk2.

Subcellular locationi

Mitochondrion matrix 1 Publication

GO - Cellular componenti

  1. mitochondrial pyruvate dehydrogenase complex Source: UniProtKB
  2. mitochondrion Source: RGD
  3. pyruvate dehydrogenase complex Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini? – 407[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrialPRO_0000023442
Transit peptidei1 – ?Mitochondrion Reviewed prediction

Proteomic databases

PaxDbiQ64536.
PRIDEiQ64536.

Expressioni

Tissue specificityi

Detected in heart (at protein level). Highest level of expression in heart and skeletal muscle and the lowest in spleen and lung. Liver, kidney, brain and testis levels are intermediate.3 Publications

Gene expression databases

GenevestigatoriQ64536.

Interactioni

Subunit structurei

Homodimer, and heterodimer with PDK1. Interacts with the pyruvate dehydrogenase complex subunit DLAT, and is part of the multimeric pyruvate dehydrogenase complex that contains multiple copies of pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (DLAT, E2) and lipoamide dehydrogenase (DLD, E3).3 Publications

Protein-protein interaction databases

IntActiQ64536. 1 interaction.
STRINGi10116.ENSRNOP00000005641.

Structurei

Secondary structure

1
407
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi13 – 153
Helixi16 – 249
Helixi33 – 397
Beta strandi41 – 433
Helixi46 – 6823
Helixi73 – 764
Helixi79 – 9618
Turni97 – 1004
Helixi106 – 12217
Turni123 – 1253
Helixi126 – 14116
Helixi145 – 17632
Beta strandi185 – 1884
Beta strandi191 – 1966
Helixi197 – 21519
Beta strandi222 – 23110
Beta strandi237 – 2404
Helixi242 – 26221
Beta strandi267 – 2693
Beta strandi273 – 2797
Beta strandi281 – 29010
Helixi297 – 3004
Helixi301 – 3044
Turni306 – 3094
Helixi329 – 33911
Beta strandi343 – 3497
Turni350 – 3523
Beta strandi353 – 36311
Turni364 – 3663
Helixi376 – 3805

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1JM6X-ray2.50A/B1-407[»]
3CRKX-ray2.30A/B1-407[»]
3CRLX-ray2.61A/B1-407[»]
ProteinModelPortaliQ64536.
SMRiQ64536. Positions 12-404.

Miscellaneous databases

EvolutionaryTraceiQ64536.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini135 – 364230Histidine kinaseAdd
BLAST

Sequence similaritiesi

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiCOG0642.
HOGENOMiHOG000164315.
HOVERGENiHBG000511.
InParanoidiQ64536.
KOiK00898.
PhylomeDBiQ64536.

Family and domain databases

Gene3Di1.20.140.20. 1 hit.
3.30.565.10. 1 hit.
InterProiIPR018955. BCDHK/PDK_N.
IPR003594. HATPase_ATP-bd.
IPR005467. Sig_transdc_His_kinase_core.
[Graphical view]
PfamiPF10436. BCDHK_Adom3. 1 hit.
PF02518. HATPase_c. 1 hit.
[Graphical view]
SMARTiSM00387. HATPase_c. 1 hit.
[Graphical view]
SUPFAMiSSF55874. SSF55874. 1 hit.
SSF69012. SSF69012. 1 hit.
PROSITEiPS50109. HIS_KIN. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q64536-1 [UniParc]FASTAAdd to Basket

« Hide

MRWFRALLKN ASLAGAPKYI EHFSKFSPSP LSMKQFLDFG SSNACEKTSF    50
TFLRQELPVR LANIMKEINL LPDRVLSTPS VQLVQSWYVQ SLLDIMEFLD 100
KDPEDHRTLS QFTDALVTIR NRHNDVVPTM AQGVLEYKDT YGDDPVSNQN 150
IQYFLDRFYL SRISIRMLIN QHTLIFDGST NPAHPKHIGS IDPNCSVSDV 200
VKDAYDMAKL LCDKYYMASP DLEIQEVNAT NATQPIHMVY VPSHLYHMLF 250
ELFKNAMRAT VESHESSLTL PPIKIMVALG EEDLSIKMSD RGGGVPLRKI 300
ERLFSYMYST APTPQPGTGG TPLAGFGYGL PISRLYAKYF QGDLQLFSME 350
GFGTDAVIYL KALSTDSVER LPVYNKSAWR HYQTIQEAGD WCVPSTEPKN 400
TSTYRVS 407
Length:407
Mass (Da):46,106
Last modified:November 1, 1996 - v1
Checksum:iA01C377290A69EF4
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U10357 mRNA. Translation: AAB54084.1.
BC061823 mRNA. Translation: AAH61823.1.
PIRiA55305.
RefSeqiNP_110499.1. NM_030872.1.
UniGeneiRn.88597.

Genome annotation databases

GeneIDi81530.
KEGGirno:81530.
UCSCiRGD:69428. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U10357 mRNA. Translation: AAB54084.1 .
BC061823 mRNA. Translation: AAH61823.1 .
PIRi A55305.
RefSeqi NP_110499.1. NM_030872.1.
UniGenei Rn.88597.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1JM6 X-ray 2.50 A/B 1-407 [» ]
3CRK X-ray 2.30 A/B 1-407 [» ]
3CRL X-ray 2.61 A/B 1-407 [» ]
ProteinModelPortali Q64536.
SMRi Q64536. Positions 12-404.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi Q64536. 1 interaction.
STRINGi 10116.ENSRNOP00000005641.

Chemistry

BindingDBi Q64536.
ChEMBLi CHEMBL2096663.

Proteomic databases

PaxDbi Q64536.
PRIDEi Q64536.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 81530.
KEGGi rno:81530.
UCSCi RGD:69428. rat.

Organism-specific databases

CTDi 5164.
RGDi 69428. Pdk2.

Phylogenomic databases

eggNOGi COG0642.
HOGENOMi HOG000164315.
HOVERGENi HBG000511.
InParanoidi Q64536.
KOi K00898.
PhylomeDBi Q64536.

Miscellaneous databases

EvolutionaryTracei Q64536.
NextBioi 615077.

Gene expression databases

Genevestigatori Q64536.

Family and domain databases

Gene3Di 1.20.140.20. 1 hit.
3.30.565.10. 1 hit.
InterProi IPR018955. BCDHK/PDK_N.
IPR003594. HATPase_ATP-bd.
IPR005467. Sig_transdc_His_kinase_core.
[Graphical view ]
Pfami PF10436. BCDHK_Adom3. 1 hit.
PF02518. HATPase_c. 1 hit.
[Graphical view ]
SMARTi SM00387. HATPase_c. 1 hit.
[Graphical view ]
SUPFAMi SSF55874. SSF55874. 1 hit.
SSF69012. SSF69012. 1 hit.
PROSITEi PS50109. HIS_KIN. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Molecular cloning of the p45 subunit of pyruvate dehydrogenase kinase."
    Popov K.M., Kedishvili N.Y., Zhao Y., Gudi R., Harris R.A.
    J. Biol. Chem. 269:29720-29724(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, FUNCTION, TISSUE SPECIFICITY.
    Tissue: Heart.
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Prostate.
  3. "Evidence for existence of tissue-specific regulation of the mammalian pyruvate dehydrogenase complex."
    Bowker-Kinley M.M., Davis W.I., Wu P., Harris R.A., Popov K.M.
    Biochem. J. 329:191-196(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: CATALYTIC ACTIVITY, ENZYME REGULATION, TISSUE SPECIFICITY.
  4. "Site specificity of four pyruvate dehydrogenase kinase isoenzymes toward the three phosphorylation sites of human pyruvate dehydrogenase."
    Korotchkina L.G., Patel M.S.
    J. Biol. Chem. 276:37223-37229(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: CATALYTIC ACTIVITY, FUNCTION.
  5. "Interaction between the individual isoenzymes of pyruvate dehydrogenase kinase and the inner lipoyl-bearing domain of transacetylase component of pyruvate dehydrogenase complex."
    Tuganova A., Boulatnikov I., Popov K.M.
    Biochem. J. 366:129-136(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH DLAT.
  6. "AZD7545, a novel inhibitor of pyruvate dehydrogenase kinase 2 (PDHK2), activates pyruvate dehydrogenase in vivo and improves blood glucose control in obese (fa/fa) Zucker rats."
    Mayers R.M., Butlin R.J., Kilgour E., Leighton B., Martin D., Myatt J., Orme J.P., Holloway B.R.
    Biochem. Soc. Trans. 31:1165-1167(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  7. "Formation of functional heterodimers by isozymes 1 and 2 of pyruvate dehydrogenase kinase."
    Boulatnikov I., Popov K.M.
    Biochim. Biophys. Acta 1645:183-192(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: CATALYTIC ACTIVITY, FUNCTION, INTERACTION WITH PDK1, SUBUNIT.
  8. "Inactivation of pyruvate dehydrogenase kinase 2 by mitochondrial reactive oxygen species."
    Hurd T.R., Collins Y., Abakumova I., Chouchani E.T., Baranowski B., Fearnley I.M., Prime T.A., Murphy M.P., James A.M.
    J. Biol. Chem. 287:35153-35160(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, ENZYME REGULATION, TISSUE SPECIFICITY.
  9. "Structure of pyruvate dehydrogenase kinase. Novel folding pattern for a serine protein kinase."
    Steussy C.N., Popov K.M., Bowker-Kinley M.M., Sloan R.B. Jr., Harris R.A., Hamilton J.A.
    J. Biol. Chem. 276:37443-37450(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH ADP.
  10. "Structural and functional insights into the molecular mechanisms responsible for the regulation of pyruvate dehydrogenase kinase 2."
    Green T., Grigorian A., Klyuyeva A., Tuganova A., Luo M., Popov K.M.
    J. Biol. Chem. 283:15789-15798(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN COMPLEX WITH ATP ANALOG AND DLAT, CATALYTIC ACTIVITY, SUBUNIT.

Entry informationi

Entry nameiPDK2_RAT
AccessioniPrimary (citable) accession number: Q64536
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: November 1, 1996
Last modified: July 9, 2014
This is version 115 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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